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Purpose: In the present study, the Poncirin was evaluated against the Paracetamol-induced liver injury using in vivo and computational approaches. Methods: The Paracetamol was administered intraperitoneally to establish the liver injury in mice and subsequently, to investigate the hepatoprotective effect of the Poncirin on the liver injury. The effect of the Poncirin was evaluated against the liver injury markers and in ammatory cytokines. Similarly, in the present study the antioxidants and oxidative stress parameters were also assessed following paracetamol-induced liver injury. The histological studies following liver injury was also assessed using H and E staining, Masson's trichrome staining, and periodic acid Schiff staining.Results: The Poncirin markedly improved the antioxidant enzymes, while attenuated the oxidative stress markers and in ammatory cytokines. The Poncirin also markedly improved hematological parameters and electrolytes pro le. Furthermore, the Poncirin treatment signi cantly improved the histological parameters using H and E staining, Masson's trichrome and PAS staining compared to the control. The Poncirin treatment also improved the liver function tests and liver synthetic activity compared to Paracetamol treated group. The immunohistochemistry analysis revealed signi cant decrease in the in ammatory signaling protein such as NF-κB (nuclear factor kappa light chain enhancer of activated B cells), JNK (Jun N-terminal Kinase) and COX-2 (Cyclooxygenase-2) expression level compared to the Paracetamol treated group. The in silico approach was also used to analyze the potential activity and explore the underlying molecular mechanism of Poncirin. Conclusion:The Poncirin improved the sign and symptoms associated with the liver injury using both in vivo and computational approaches.

Multiple sclerosis (MS) is a debilitating neurodegenerative autoimmune disease of the central nervous system (CNS). The current study aimed to investigate the neuroprotective properties of Ajugarin-I (Aju-I) against the experimental autoimmune encephalomyelitis (EAE) model of MS and explored the underlying mechanism involved. The protective potential of Aju-I was first confirmed against glutamateinduced HT22 cells and hydrogen peroxide (H 2 O 2 )-induced BV2 cells. Next, an EAE model has been established to investigate the mechanisms of MS and identify potential candidates for MS treatment. The behavioral results demonstrated that Aju-I post-immunization treatment markedly reduced the EAE-associated clinical score, motor impairment, and neuropathic pain. Evans blue and fluorescein isothiocyanate extravasation in the brain were markedly reduced by Aju-I. It effectively restored the EAE-associated histopathological changes in the brain and spinal cord. It markedly attenuated EAE-induced inflammation in the CNS by reducing the expression levels of p-38/JNK/NF-κB but increased the expression of IkB-α. It suppressed oxidative stress by increasing the expression of Nrf2 but decreasing the expression of keap-1. It suppressed EAE-induced apoptosis in the CNS by regulating Bax/Bcl-2 and Caspase-3 expression. Taken together, this study suggests that Aju-I treatment exhibits neuroprotective properties in the EAE model of MS via regulation of MAPK/ NF-κB, Nrf2/Keap-1, and Bcl2/Bax signaling.